Dr. Jeff Hersh: Understanding porphyria

Q: My sister has had several bouts of severe abdominal pain of unknown cause in the last few years. They now think these were from porphyria. What is this?

Dr. Jeff Hersh

Q: My sister has had several bouts of severe abdominal pain of unknown cause in the last few years. They now think these were from porphyria. What is this?

A: The different types of porphyria (cutaneous or acute) occur because of a defect in one of the heme-synthesizing enzymes. Heme is made in essentially all of the body's tissues, but primarily in the bone marrow (accounting for about 80 percent; here it is mostly used to make hemoglobin for red blood cells) and the liver (accounting for almost all the rest and used to make certain liver enzymes). The defect in heme synthesization causes an accumulation of one of the heme precursors (porphyrins); when they acutely build up they can cause toxicity to the nerves and/or skin.

Many people with porphyria never manifest symptoms, but for those who do, symptomatic attacks usually begin in adulthood, typically between ages 20 to 40. Diagnosis of porphyria is made by screening for excesses of porphyrins (porphobilinogen or delta-aminolevulinic aid) during an acute attack. Elevated amounts of these can be found in urine, stool and/or (for some types of porphyria) blood. When suspicion of porphyria is high or there is a positive screening test during an acute attack, further testing is indicated. DNA evaluation may be done to identify the specific defect in a given patient.

Since the porphyrias cause only a partial enzyme defect, there is often a trigger that causes symptoms to manifest. Common triggers include certain medications, certain chemical exposures, stress, surgery, alcohol, sun exposure, smoking, infections, iron overload or many others.

Cutaneous porphyria manifests as skin oversensitivity to light, causing itch, redness and swelling. The most common of these (affecting about 1 in 25,000 Americans) is called porphyria cutanea tarda and also causes blistering of the skin. About 80 percent of the cases of porphyria cutanea tarda are "sporadic" (not inherited), with the other 20 percent being inherited in an autosomal dominant fashion (you only need to inherit one copy of the gene to have the condition).

The less common cutaneous porphyria erythropoietic protoporphyria does not cause blistering; it is also an autosomal dominant inherited condition.

Some patients with cutaneous porphyria having ongoing symptoms will benefit from phlebotomy to reduce iron stores; this can help induce a remission. Activated charcoal (to absorb some of the porphyrins) and vitamin A can also be helpful. Of course, these patients should also avoid sun exposure and any other symptom triggers. Cutaneous porphyrias can cause long-term skin damage.

The most common symptom of the acute porphyrias is abdominal pain -- which affects about 90 percent of symptomatic patients -- due to toxicity to the visceral nerves. The abdominal pain of acute porphyria is typically severe and out of proportion to the physical exam (the patient is usually not tender to palpation), crampy in nature and often accompanied by vomiting, constipation and/or distention.

When peripheral nerves are affected from an acute porphyria, the patient may have pain and/or numbness in the arms, legs, chest and/or back. Autonomic nerve involvement can affect blood pressure and/or heart rate. Involvement of the central nervous system can cause seizures, neuropsychiatric symptoms and even electrolyte abnormalities (from effects to certain controlling hormones made in the brain). Many other symptoms, depending on the nerves affected, can occur as well. The most common acute porphyria, acute intermittent porphyria, is inherited in a dominant fashion and affects about 1 in 200,000 Americans.

Patients with acute porphyrias can minimize attacks by avoiding their triggers. During an acute attack, they will often need to be hospitalized for treatments such as pain medication, correction of any electrolyte imbalance, IV fluids for dehydration, and IV glucose and injections of hemin or hematin (forms of heme) to decrease their body's need to make heme. Attacks of acute porphyria can be life-threatening. Over time, multiple attacks can affect the liver, kidney and possibly other organs.

Unexplained attacks of severe abdominal pain should have acute porphyria considered as a possible diagnosis. Patients with porphyria should be sure all their health care providers are aware of their condition (so medications that may trigger an attack can be avoided), and should wear a Medic Alert bracelet.

People should be sure their health care providers know of any family history of porphyria so the diagnosis will be considered for any symptoms that can come from this disease.